Abstract IA15: VEGF-targeted therapies: Biomarkers, biology, and understanding resistance

Despite major advances in the clinical development of VEGF-targeted therapy, most patients9 tumors are considered to be inherently resistant. When response is obtained, the benefit of VEGF inhibitors is transient, lasting weeks to months, in contrast to the original hypothesis that cancer would be converted to a chronic disease with this therapeutic approach. The mechanisms of action of this class of drugs vary among tumor types and therefore resistance mechanisms and biomarkers are likely to be tumor-type specific. Clinical studies have begun to uncover potential biomarkers that require validation in prospective studies. For example, data reported at the 2011 ESMO meeting suggested that circulating VEGF, as detected by a new ELISA, may be able to determine the population of patients likely to benefit from the use of bevacizumab, in some, but not all studies. In addition, several clinical studies reported this past year have shown that continued VEGF-inhibition through multiple lines of therapy may be of benefit to patients. These clinical studies suggest that resistance may be a relative term: although patients eventually progress, continued VEGF inhibition beyond initial progression may be of clinical benefit in selected patients. There is much work to be done in the field of biomarkers for VEGF-targeted therapies, but these recent clinical studies provide insights that will hopefully provide the foundation for significant improvements in patient outcomes.